Polymer Chemistry - Ring-Opening-Polymerisation (ROP)

Polymer Chemistry - Ring-Opening-Polymerisation (ROP)

Aims of this part: General Mechanism Polyesters from Ring-Opening Polymerisation Formation of Nylon 6 (and similar) Polymerisation of N-Carboxy-Anhydrids (NCAs) Cationic Ring-Opening Polymerisation Ring-Opening Metathesis Polymerisation (ROMP) Radical Ring-Opening Polymerisation (RROP) Braun, Chedron, Rehann, Ritter, Voit Polymer Synthesis: Theory and Practice, Springer, 5 th Edition, 2013. Sections 3.2, 3.3 Lechner, Gehkre, Nordmeier, Makromolekulare Chemie, Springer, 5 th Edition, 2014. Sections 3.1, 3.2

Mechanism + Monomers: Overview on the method Initiator Living Polymerisation: Continuous growth of polymer Continuous growth of molecular weight Controlled polymerisation technique (low dispersity values) p Growth of Molecular Mass Chain growth For controlled polymersiation u

Polyesters - PCL ROP: Lactones give Polyesters of many molecular weights Poly-e-caprolactone (PCL) Anionic: Alcoholate opens first ring Continueation Cationic: Carbonyl-O attacks ring in Sn2 Reaction (rarely done) Enzymatically: Lipase (Candida antartica lipase B, CALB) = Novozym 435 (if immobilised on acrylic resin) Applications of PCL: Additive for Polyolefines (better colouring) Copolymer in drug delivery for time-delayed drug release Nanoparticles for the homopolymer, also for drug delivery PCL has a T g of 60 C hindering some applications. Introduction of PmCL

Polyamides Nylon 6 ROP: Lactames give polyamides Number of C-Atoms stated in name Poly-e-caprolactame = Nylon 6 Anionic: Deprotonated amide attacks the next ring Cationic: Carbonyl-O attacks ring in Sn2 Reaction (rarely done) High molecular weights possible, but transamidation shortens the polymer with ongoing reaction time. Reaction is seldomly complete, monomer always present Larger Ring equillibrium shifted towards the polymer Like other polymides, very important fibre material! Also technical material for foils and larger items then done in bulk in the final form (e.g. Propellers of ships)

NCA-Polymerisation Non-ionic ROP with the loss of CO 2 Monomers: N-Carboxy-Anhydrides (NCAs) Leuchs-anhydrides Phosgen commonly substituted by other CO source Nylon 2 (Name not used) Polypeptoid if R on nitrogen, H on carbon 1 carbon a-polypeptoid, 2 carbons b-polypeptoid Polypeptide if R on carbon, H on nitrogen Important for research on peptides and peptoids as well as synthetic homopolypeptides (pharmaceutical industry)

Group of Robert Luxenhofer, Uni Würzburg Polypeptoids Highly controlled reaction: Final amine can be re-used as macroinitiator Block-Copolymers and self-assembly Mn = 21800 Đ = 1.17 Macromolecules 2011, 44, 6746 6758; Macromol. Rapid Commun. 2012, 33, 1708 1713; Scientific Reports, 2016, 6, 33491

Excursion: Solid Phase Synthesis Highly controlled reaction Monomers added (sub)sequentially Possible for Polypepoids (shown here) and Polypeptides Developed by R. Zuckermann, Berkley Block-co-oligopeptoids for self-assembly Mn = 1736 Đ = 1.004 Low dispersity! 1500 1800 2100 Mass (Da)

Nucleophilic attac of cyclic ethers Polyether El electrophile (cationic), Nu nucleophile (anionic) H: PEG / PEO Poly-THF (long diol for PUR!) Me: PPG PEG is of high importance for the pharmaceutical industry: PEG is biocompatible but NOT biodegradable Prolonged circulation of proteins or drugs in the blood if decorated with PEG stealth effect Easily accessible and low dispersity (know what you have) Problem: PEG-antibodies have been reported PEG is still the most popular hydrophilic polymer

PEG in research PEG is the most prominent hydrophilic polymer in current biomedical research PEGylation has become its own term Screenshot from iris biotech (PEG provider): High use for block-copolymers initiators for all current polymerisation methods are commercially available in all lengths and with low dispersity What would be an alternative? Polysarcosin (Me-Polypeptoid), Polymethyloxazoline but not much more!

Cationic Ring Opening for Oxazolines Poly-2-oxazolines are quasi-polyamides Typical initiator: Tosylates, Triflates, Lewis acids, alkyl chloroformates Hydrophilicity depends on the side chain: Me Hydrophilic; Et, ipr amphiles/responsive (LCST), longer: hydrophobic Key information: PMOxa is FDA approved and as such widely applied Wide range of functionalization + application is possible Wide range of molecular weights can be reached (up to 250 kg/mol) Although FDA approved and versatile, no clinical application is known and bioconjugates are rarely researched upon

Metathesis Polymerisation (ROMP) Fabrication of aliphatic polymers with repeating trans double bonds in the main chain Mechanism: Catalysts: Grubbs I Schrock (also W) Grubbs II Chem. Rev. 2010, 110, 1746 1787

Metathesis Polymerisation (ROMP) Polymerisation tolerates functional units (OH, amines (lesser extent)) Stereocentres can be included in a specific way Some catalysts can induce homogeneous stereocentres Starting from an R/S mixture only one can polymerise! All catalysts have a different reactivity depending on metal centre / ligands Grubbs cat. Tolerates most ligands great variety in reactivity Hoyveda-Grubbs catalysts have Hoyveda-Grubbs II largest stability reported Chem. Rev. 2010, 110, 1746 1787

Radical Ring-Opening Polymerisation A polyester from a radical polymerisation! Cyclic ketene acetal (CKA) Accepted mechanism of the reaction X = OH (for CKAs) - formation of polyesters X = NH (for CKAAs) - formation of polyamides A. Tardy, J. Nicolas, D. Gigmes, C. Lefay and Y. Guillaneuf, Chem. Rev., 2017, DOI: 10.1021/acs.chemrev.6b00319 S. Agarwal, Polym. Chem., 2010, 1, 953-964 W. J. Bailey, Z. Ni and S. R. Wu, J. Polym. Sci., Part A: Polym. Chem., 1982, 20, 3021-3030

Radical Ring-Opening Polymerisation Monomer Synthesis: Route choice depending on monomer Known monomers

Summary Polyesters and Polyamides can also be made via ROP. Nylon 6 and PCL are important examples. NCA-Polymerisation gives Polypeptides and Polypeptoids. Is a highly controlled polymerisation technique that involves no ions. Oligomers of this kind can be reached very clean in solid phase synthesis. ROP of cyclic ethers gives PEG (besides others). PEG is a highly important biomedical polymer (biostable, biocompatible) Polyoxazolines are quasi-polyamides. (Amide in sidechain) Hydrophobicity can be tuned by length of side chain Metathesis polymerisation yields polyolefins with double bond Catalyst can be made tolerant towards a number of reactive groups Radical Ring-Opening Polymerisation yields a polyester, but can tolerate nucleophilic side groups